The Challenges of Vaccine Development against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Po
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The Challenges of Vaccine Development against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector T. A. Zaichuka, Y. D. Nechipurenkob, *, A. A. Adzhubeyb, c, S. B. Onikienkod, V. A. Chereshneve, S. S. Zainutdinovf, G. V. Kochnevaf, S. V. Netesovg, and O. V. Matveevaa, h, ** aSendai
Viralytics, Acton, MA, 117261 USA Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia cGeorge Washington University, Washington, DC, 20052 USA dDepartment of Military Field Therapy, Kirov Military Medical Academy, St. Petersburg, 194044 Russia eInstitute of Immunology and Physiology, Yekaterinburg, 620049 Russia fState Research Center of Virology and Biotechnology “Vector,” Koltsovo, 630559 Russia gDepartment of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090 Russia hBiopolymer Design, Acton, MA, 117281 USA *e-mail: [email protected] **e-mail: [email protected] bEngelhardt
Received April 30, 2020; revised June 4, 2020; accepted June 5, 2020
Abstract—To design an effective and safe vaccine against betacoronaviruses, it is necessary to use their evolutionarily conservative antigenic determinants that will elicit the combination of strong humoral and cellmediated immune responses. Targeting such determinants minimizes the risk of antibody-dependent enhancement of viral infection. This phenomenon was observed in animal trials of experimental vaccines against SARS-CoV-1 and MERS-CoV that were developed based on inactivated coronavirus or vector constructs expressing the spike protein (S) of the virion. The substitution and glycosylation of certain amino acids in the antigenic determinants of the S-protein, as well as its conformational changes, can lead to the same effect in a new experimental vaccine against SARS-CoV-2. Using more conservative structural and accessory viral proteins for the vaccine antigenic determinants will help to avoid this problem. This review outlines approaches for developing vaccines against the new SARS-CoV-2 coronavirus that are based on non-pathogenic viral vectors. For efficient prevention of infections caused by respiratory pathogens the ability of the vaccine to stimulate mucosal immunity in the respiratory tract is important. Such a vaccine can be developed using non-pathogenic Sendai virus vector, since it can be administered intranasally and induce a mucosal immune response that strengthens the antiviral barrier in the respiratory tract and provides reliable protection against infection. Keywords: SARS-CoV-2, SARS-CoV-1, COVID-19, antibody-dependent enhancement, ADE, vaccine vector, Sendai virus, murine respirovirus, conservative antigenic determinants DOI: 10.1134/S0026893320060151
The vaccine approaches for COVID-19 are extremely diverse. This review analyzes the problems encountered in creating vaccines targeting SARS-CoV-2. In addition, non-pathogenic viral vectors for the expression of antigenic determinants of this virus have been examined. We present arguments in favor of the application of th
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